mTOR Signaling Regulates Multiple Metabolic Pathways in Human Lung Fibroblasts After TGF-β and in Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis is a fatal disease characterized by the TGF-β-dependent activation of lung fibroblasts, leading to excessive deposition of collagen proteins and progressive replacement of healthy lung with scar tissue. We and others have shown that TGF-β-mediated activation of the Mechanistic Target of Rapamycin Complex 1 (mTORC1) and downstream upregulation of Activating Transcription Factor 4 (ATF4) promote metabolic reprogramming in lung fibroblasts characterized by upregulation of the de synthesis of glycine, the most abundant amino acid found in collagen protein. Whether mTOR and ATF4 regulate other metabolic pathways in lung fibroblasts has not been explored.

Bound-State Beta Decay of ^{205}Tl^{81+} Ions and the LOREX Project.

Stable ^{205}Tl ions have the lowest known energy threshold for capturing electron neutrinos (ν_{e}) of E_{ν_{e}}≥50.6  keV. The Lorandite Experiment (LOREX), proposed in the 1980s, aims at obtaining the longtime averaged solar neutrino flux by utilizing natural deposits of Tl-bearing lorandite ores.

Role of Arginine and its Metabolism in TGF-β-Induced Activation of Lung Fibroblasts.

Arginine is a conditionally essential amino acid with known roles in protein production, nitric oxide synthesis, biosynthesis of proline and polyamines, and regulation of intracellular signaling pathways. Arginine biosynthesis and catabolism have been linked to TGF-β-induced activation of fibroblasts in the context of pulmonary fibrosis; however, a thorough study on the metabolic and signaling roles of arginine in the process of fibroblast activation has not been conducted. Here, we used metabolic dropouts and labeling strategies to determine how activated fibroblasts utilize arginine.

Sustained hypoxia but not intermittent hypoxia induces HIF-1α transcriptional response in human aortic endothelial cells.

Obstructive sleep apnea (OSA) is characterized by intermittent hypoxic environments at the cellular level and is an independent risk factor for the development of cardiovascular disease. Endothelial cell (EC) dysfunction precedes the development of cardiovascular disease; however, the mechanisms by which ECs respond to these intermittent hypoxic events are poorly understood. To better understand EC responses to hypoxia, we examined the effects of sustained hypoxia (SH) and intermittent hypoxia (IH) on the activation of HIF-1α in ECs.

HIF-1α regulates mitochondrial function in bone marrow-derived macrophages, but not in tissue-resident alveolar macrophages.

HIF-1α plays a critical role in shaping macrophage phenotype and effector function. We have previously shown that tissue-resident alveolar macrophages (TR-AMs) have extremely low glycolytic capacity at steady-state, but can shift toward glycolysis under hypoxic conditions. Here, using inducible HIF-1α knockout ( ) TR-AMs and bone marrow-derived macrophages (BMDMs) and show that TR-AM HIF-1α is required for the glycolytic shift under prolyl hydroxylase inhibition, but is dispensable at steady-state for inflammatory effector function.

Effects of age on human skeletal muscle: a systematic review and meta-analysis of myosin heavy chain isoform protein expression, fiber size, and distribution.

Human studies examining the cellular mechanisms behind sarcopenia, or age-related loss of skeletal muscle mass and function, have produced inconsistent results. A systematic review and meta-analysis were performed to determine the aging effects on protein expression, size, and distribution of fibers with various myosin heavy chain (MyHC) isoforms. Study eligibility included MyHC comparisons between young (18-49 yr) and older (≥60 yr) adults, with 27 studies identified.

Welfare status of dairy cows reared from large scale dairy farms in Midlands Province -Zimbabwe.

In Zimbabwe a lot of studies have been done on nutrition, breeding, physiology and health of farm cows but with little or no consideration of the impacts of these studies on cow welfare. As a result political importance and practical progression of cow welfare is still lagging behind in the country just like most developing countries. The aim of this study was to evaluate the welfare status of dairy cows from large scale dairy farms through an assessment of risk factors/drivers and indicators of cow welfare.

Evaluating a Mobile App Supporting Evidence-Based Parenting Skills: Thematic Analysis of Parent Experience.

Background: Disruptive behavior disorders are among the most common disorders of childhood, and evidence-based parenting programs are the first-line treatment. Digital microinterventions have been proposed as one possible means of supporting parenting style change by giving parents in-the-moment advice about how to respond to challenging behavior. Until now, no digital microintervention supporting evidence-based parenting skills programs has been evaluated.

Shedding Light on the Origin of ^{204}Pb, the Heaviest s-Process-Only Isotope in the Solar System.

Asymptotic giant branch stars are responsible for the production of most of the heavy isotopes beyond Sr observed in the solar system. Among them, isotopes shielded from the r-process contribution by their stable isobars are defined as s-only nuclei. For a long time the abundance of ^{204}Pb, the heaviest s-only isotope, has been a topic of debate because state-of-the-art stellar models appeared to systematically underestimate its solar abundance.

A Scoping Review of Patient Involvement in Violence Risk Assessment.

Objective: This scoping review aimed to summarize the published literature on patient involvement in violence risk assessment. Two research questions reviewed the extent of patient involvement and what evidence exists.

Inclusion Criteria: English-language peer-reviewed published articles of any methodology related to violence risk assessment toward others were included.

A Digital Microintervention Supporting Evidence-Based Parenting Skills: Development Study Using the Agile Scrum Methodology.

Background: Conduct disorder increases risks of educational dropout, future mental illness, and incarceration if untreated. First-line treatment of conduct disorder involves evidence-based parenting skills programs. Time-outs, a frequent tool in these programs, can be effective at improving behavior, and recent apps have been developed to aid this process.

ATF4 and mTOR regulate metabolic reprogramming in TGF-β-treated lung fibroblasts.

Idiopathic pulmonary fibrosis is a fatal disease characterized by the TGF-β-dependent activation of lung fibroblasts, leading to excessive deposition of collagen proteins and progressive replacement of healthy lung with scar tissue. We and others have shown that fibroblast activation is supported by metabolic reprogramming, including the upregulation of the synthesis of glycine, the most abundant amino acid found in collagen protein. How fibroblast metabolic reprogramming is regulated downstream of TGF-β is incompletely understood.

Astronomy's climate emissions: Global travel to scientific meetings in 2019.

Travel to academic conferences-where international flights are the norm-is responsible for a sizeable fraction of the greenhouse gas (GHG) emissions associated with academic work. In order to provide a benchmark for comparison with other fields, as well as for future reduction strategies and assessments, we estimate the CO-equivalent emissions for conference travel in the field of astronomy for the prepandemic year 2019. The GHG emission of the international astronomical community's 362 conferences and schools in 2019 amounted to 42,500 tCOe, assuming a radiative-forcing index factor of 1.

Measurement of the ^{140}Ce(n,γ) Cross Section at n_TOF and Its Astrophysical Implications for the Chemical Evolution of the Universe.

^{140}Ce(n,γ) is a key reaction for slow neutron-capture (s-process) nucleosynthesis due to being a bottleneck in the reaction flow. For this reason, it was measured with high accuracy (uncertainty ≈5%) at the n_TOF facility, with an unprecedented combination of a high purity sample and low neutron-sensitivity detectors. The measured Maxwellian averaged cross section is up to 40% higher than previously accepted values.

Too risky to use, or too risky not to? Lessons learned from over 30 years of research on forensic risk assessment with Indigenous persons.

Indigenous peoples are overrepresented in correctional systems internationally, reflecting a history of systemic racism and colonial oppression, and the practice of risk assessment with this population has been a focus of legal and sociopolitical controversy. We conducted a systematic review and meta-analysis of the risk assessment literature comparing Indigenous and non-Indigenous (White majority) groups. We retrieved 91 studies featuring 22 risk tools and 15 risk/need/cultural domains ( = 59,693, Indigenous; = 237,729, non-Indigenous/White) and four documents identifying culturally relevant factors.

Strategies for secondary use of real-world clinical and administrative data for outcome ascertainment in pragmatic clinical trials.

Background: Pragmatic trials are gaining popularity as a cost-effective way to examine treatment effectiveness and generate timely comparative evidence. Incorporating supplementary real-world data is recommended for robust outcome monitoring. However, detailed operational guidelines are needed to inform effective use and integration of heterogeneous databases.

PRG4 deficiency in mice alters skeletal structure, mechanics, and calvarial osteoclastogenesis, and rhPRG4 inhibits in vitro osteoclastogenesis.

Osteoporosis is a chronic disease characterized by reduced bone mass and increased fracture risk, estimated to affect over 10 million people in the United States alone. Drugs used to treat bone loss often come with significant limitations and/or long-term safety concerns. Proteoglycan-4 (PRG4, also known as lubricin) is a mucin-like glycoprotein best known for its boundary lubricating function of articular cartilage.

Simplified urine-based method to detect rifampin underexposure in adults with tuberculosis: a prospective diagnostic accuracy study.

Variable pharmacokinetics of rifampin in tuberculosis (TB) treatment can lead to poor outcomes. Urine spectrophotometry is simpler and more accessible than recommended serum-based drug monitoring, but its optimal efficacy in predicting serum rifampin underexposure in adults with TB remains uncertain. Adult TB patients in New Jersey and Virginia receiving rifampin-containing regimens were enrolled.

Loss of heme oxygenase 2 causes reduced expression of genes in cardiac muscle development and contractility and leads to cardiomyopathy in mice.

Obstructive sleep apnea (OSA) is a common breathing disorder that affects a significant portion of the adult population. In addition to causing excessive daytime sleepiness and neurocognitive effects, OSA is an independent risk factor for cardiovascular disease; however, the underlying mechanisms are not completely understood. Using exposure to intermittent hypoxia (IH) to mimic OSA, we have recently reported that mice exposed to IH exhibit endothelial cell (EC) activation, which is an early process preceding the development of cardiovascular disease.